Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study.

OBJECTIVE: Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. SUBJECTS: We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. RESULTS: FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284). CONCLUSION: FTO genotype is an independent risk factor for future development of obesity.

[A case report of successful open valvotomy in neonate with critical aortic stenosis].

Open valvotomy was successfully performed in neonate with critical aortic stenosis using cardiopulmonary bypass. The baby was referred to our hospital at the age of 24 days with very grave state, and needed intensive care including endotracheal intubation and inotropic support. Critical valvular aortic stenosis was confirmed by echocardiography. Poststenotic dilatation and enough size of short axis LV dimension were reported, and aortic annulus was measured 6 mm in diameter. Without catheterization and angiography, open valvotomy was performed with moderate hypothermia and ischemic arrest using single dose of cold cardioplegia at the age of 29 days. Bicuspid aortic valve was thick and dysplastic with thick gelatinous cusp edge, however commissurotomy was applicable in two direction. The diameter of aortic opening was enlarged from 2 mm to 7 mm. Total bypass and aortic cross clamp time were 78 and 28 minutes respectively. The baby recovered uneventfully and there was no evidence of significant AS or aortic regurgitation in echocardiography 7 months after surgery. Sorts of reoperation for restenosis or regurgitation were reported. The results of reoperation for regurgitation were reported to be poor, especially in young infants who should be performed aortic valve replacement. However, residual AS could be manipulated with re-valvotomy, PVB, apico-aortic conduit or AVR. As the choice of first relief of critical AS without other anatomical disadvantages including hypoplastic left ventricle, endocardial fibroelastosis, and mitral stenosis, it would be crucial for late results to prevent progression of aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)